Hormone Physiology, Biochemistry and Functions

Objectives of the Material

• The material will review the physiology, biochemistry, and functions of hormones, particularly in the steroidogenic pathway
• The pros and cons of hormone replacement are discussed
• Functions of melatonin and its relationship with insulin and other hormones will be reviewed
• The interplay among adrenal hormones, estrogen, progesterone, and testosterone is explained

Continuing Education Accreditation

• AKH Inc., Advancing Knowledge in Healthcare and Precision Medicine Consultants jointly provide the activity.
• Jointly accredited by ACCME, ACPE, and ANCC.
• Physicians can earn a maximum of 24.0 AMA PRA Category 1 Credit(s).
• Hours of participation equate to the number of AMA PRA Category 1 Credit(s) awarded.
• There is no commercial support for the activity.
• The fee to participate is $2,700.00
• A certificate is issued after attendance and completing an online evaluation/claim credit form
• The deadline to apply for credit is December 17, 2024.

Menopause

• Hormone response is unique like fingerprints.
• Hormone replacement should only be considered with a deep understanding of hormonal interactions
• The normal age range of 35 to 55
• Women may live half their lives without a menstrual cycle.
• Cycling after 55 increases a woman's risk of breast cancer.

HRT Considerations

• HRT can provide relief of symptoms for the patient
• It can prevent memory loss
• Can aid in the heart health
• Helps in bone production
• Aids in Growth and repair of the body

Synthetic HRT Issues

• About half of women stop taking synthetic hormone replacement therapy after one year due to side effects.
• Synthetic hormones provide incomplete messages to cells, leading to an unbalanced hormonal response and wasted energy.

Hormones Regulating Growth and Repair

• Insulin
• Growth hormone
• Testosterone
• Estrogens
• DHEA

Menopause Symptoms

• Hot flashes, night sweats, vaginal dryness
• Anxiety, mood swings, irritability, insomnia, depression
• Loss of sexual interest, hair growth on face, painful intercourse
• Panic attacks, weird dreams, urinary tract infections, vaginal itching
• Lower back pain, bloating
• Flatulence, indigestion, osteoporosis
• Aching joints (ankles, knees, wrists, shoulders, heels), hair loss
• Frequent urination, snoring, sore breasts
• Palpitations, varicose veins, urinary leakage
• Dizzy spells, skin feeling crawly, migraine headaches, memory lapses, weight gain

Estrogen

• Estrogen has 400 functions in the body.
• Functions include stimulating choline acetyltransferase production to prevent Alzheimer's.
• It can increase metabolic rate, improve insulin sensitivity, regulate body temperature, and improve sleep.
• It can reduce the risk of cataracts, help maintain artery elasticity, and increase blood flow, and inhibit platelet stickiness
• Decreases plaque accumulation, enhances magnesium use, maintains skin collagen, reduces blood pressure, prevents LDL oxidation
• Can helps maintain memory, reasoning, motor skills, and skin thickness
• Enhance nerve-growth factor production, and overall have a positive effect on emotions
• Increases HDL by 10-15%, reduces heart disease risk by 40-50%, decreases lipoprotein(a)
• Acts as a calcium channel blocker, enhances energy, improves mood and concentration
• Maintains bone density, helps prevent glaucoma
• Increases sexual interest, reduces homocysteine, decreases wrinkles
• Protects against macular degeneration, and colon cancer, prevents tooth loss
• Aids neurotransmitter formation and decreases depression, irritability, anxiety, and pain sensitivity

Symptoms of Estrogen Excess

• Cervical dysplasia, depression with anxiety, uterine cancer
• Weight gain, water retention, headaches, poor sleep, and panic attacks
• Heavy periods, the potential for breast cancer and autoimmune diseases
• Hypothyroidism, fatigue, and it can cause irregular mood swings and bloating

Causes of Excess Estrogen

• Taking too much estrogen
• Impaired elimination of estrogen
• Lack of exercise
• Diets low in grains and fiber
• Environmental estrogens

Synthetic Estrogen

• Synthetic estrogen differs chemically from the estrogen produced naturally in the body.
• Common synthetic estrogens are available worldwide
• Including estrone and sodium equilin sulfate
• With concomitant components like 17 alpha-dihydroequilin, 17 alpha-estradiol, and 17 beta-dihydroequilin.

Natural Estrogen

• Medically having the same chemical structure that is naturally in the patients body
• It may or may not be plant-derived.
• Helps to protect against endothelial dysfunction by increasing endothelial nitric oxide.

Natural Estrogen Continued

• Endothelial nitric oxide synthase is a crucial enzyme in nitric oxide production in endothelial cells.
• Compared to natural estrogen, gene transcription of endothelial nitric oxide synthase was 30-50% lower in response to equine estrogens.

Estradiol and Estriol

• E1 is called estrone.
• E2 is called estradiol.
• E3 is called estriol.

Estrone (E1)

• Is the main estrogen produced in postmenopausal women.
• Elevated levels are thought to increase one's risk of breast cancer.

Estradiol (E2)

• It increases HDL and decreases LDL, along with total Triglycerides and cholesterol.
• Helps maintain bone structure.
• Increases serotonin and decreases fatigue.
• Works as an antioxidant.
• Helps maintain memory.
• Helps increase absorption of calcium, zinc, and magnesium.
• Can directly reduce atherosclerosis by controlling the cholesterol accumulation in arteries

Estriol (E3)

• Is 80 times weaker than E2 so there is less stimulatory effect
• Extensive data shows that it protects against breast cancer and is being used in breast cancer patients as treatment in some instances.
• Doesn’t offer the same protection to bone, heart, or brain like estradiol does.

Functions of E3

• Helps maintain pregnancy and benefits the vaginal lining.
• Blocks E1 by occupying the estrogen receptor sites on the cells of the breasts.
• Can control symptoms of menopause.
• Lowers LDL.
• Increases HDL.
• Can reduce pathogenic bacteria

Functions of E3 Continued

• Helps to restore vaginal pH and therefore prevents urinary tract infections.
• The GI tract also is maintained by it and a stable environment is there for growth of lactobacilli.
• Shows that it has potential immunomodulatory benefits for a multitude of diseases like inflammatory, neurodegenerative, and autoimmune conditions.

Estrogen Receptor Sites

• Estrogen binds to two receptor types
  • Estrogen receptor alpha
    • Increases undesirable growth in reproductive tissues.
  • Estrogen receptor beta
    • Decreases cell growth.
    • Helps to prevent breast cancer.
    • Promotes beneficial estrogenic effects on skin, bone, brain, and other tissues.

Estrogen Receptor Sites Continued

• E2 equally activates estrogen-receptors alpha and beta.
• E1 activates estrogen-receptor alpha selectively in a 5:1 ratio, which increases cell proliferation.
• E3 binds preferentially to estrogen-receptor beta in a 3:1 ratio, possibly preventing breast cancer.
• Siberian rhubarb has been shown to activate estrogen receptor ER-beta to a greater extent than ER-alpha receptors.

Estrogen Metabolism

• Estrogen metabolism can change after menopause, with a different response to estrogen replacement.
• Has two major competing pathways: 2-OH estrone & 16-OH estrone.
• One Minor pathway 4-OH estrone

2-OH Estrone

• It is a good estrogen that does not stimulate cell growth.
• Blocks action of carcinogenic estrogen products.
• It is protective against cancer when methylated by catechol-O-methyltransferase (COMT) into 2-methoxy-estrone.
• 2-methoxyestrone and 2-hydroxyestrone ratios are measured in urine and is used to guage the body in its process of methylation.

2-OH Estrone/Methylation Continued

• Evaluating the body's ability to methylate is measuring by observing the homocysteine level.
• Low ratios of 2/16 hydroxy estrogen often point to an increased lupus rate.

Factors Supporting Methylation

• SAMe
• Methionine
• B2, B6, B12
• Folic acid
• TMG (betaine)
• Reducing catecholamine production by decreasing stress

16-OH Estrone

• Has significant strong estrogenic activity, and may be linked to an increased breast cancer risk.
• High levels are tied to obesity, pesticide toxicity, hypothyroidism, omega-6-fatty acid excess, and inflammatory cytokines.

4-OH Estrone

• It can damage DNA and cause mutations, therefore enhancing possibilities for cancer to develop.
• Equine estrogens like Premarin, increase the metabolism into 4-OH estrones.
• When more 4-OH estrone is present in greater quantities there is commonly a deficiency of methionine and folic acid.
• Increased levels of 4-OH estrone in People who have uterine fibroids.

Increasing 2-OH Estrone

• Moderate exercise
• Cruciferous vegetables
• Flax
• Soy
• Kudzu
• Broccoli derivatives such as I3C with a daily dosage of 200mg to 300mg

Increasing 2-OH Estrone Continued

• Omega-3 fatty acids
• B6, B12, and folate
• MTHF
• TMG
• Rosemary, turmeric
• Weight loss
• High protein diet

Obesity Affecting Estrogen Metabolism

• It decreases 2-OH estrone and increases 16-OH estrone.
• Estrogen production and storage occurs in fat cells.
• Concentrations of sex hormone binding globulin (SHBG) are decreased.

Xenoestrogens

• These 50 chemicals can damage the body by imitating estrogen.
  • With sources being pesticides, synthetic hormones in animals, plastics, and cosmetics

Alcohol

• Alcohol interferes with the body's ability to detoxify estrogen, which can lead to high E2 levels and the potential for breast cancer

Antibiotics

• May potentially be associated with elevated breast cancer risk by impacting the gut flora in enterohepatic circulation of estrogens.

Estrogen and the Brain

• Some common symptoms that are conveyed are feelings of disconnect, memory loss, losing items, and fears of Alzheimer's.
• Increases blood flow, glucose, and oxygen to areas in the neurons.
• It can keep the blood-brain barrier working and protect the neurons.
• By decreasing neuronal generation of Alzheimer's beta-amyloid peptides.

Estrogen and the Brain Continued

• Is a natural antioxidant that increases manual speed, dexterity and availability of other compounds
• Boosts NMDA receptors to help strength and durability in synapse connections for long-term memory
• Decreases distractibility by tuning on progesterone receptors.

Estrogen and the Heart

• Starting menopausal hormone treatment (MHT) within 5 to 10 years of menopause is fundamental to the success of estrogen's cardioprotection in post-menopausal women without adverse effects.
• HRT improves atherosclerosis and survival for various calcium levels.

Estrogen and Hypertension in Women

• Menopause is associated through a rise in hypertension, leading to endogenous estradiol.
• Oral estrogen can increase blood pressure, however, so transdermal is better.
• Can play more of a role with hypertension in systemic areas.

Estrogen and Heart Failure

• Cardiac estrogen is reduced in heart failure.
• Estrogen supplementation can help by restoring and stimulating different processes.

Estrogen and Memory

• HRT can contribute to good cognitive outcomes after menopause with an obesogenic diet
• Studies showed women in their 50s had lower mortality rates than those not taking any estrogen supplements

Estrogen and Bone Health

• It improves BMD for women, and the estrogen should be transdermally not orally prescribed for the job.

Estrogen and Cataracts

• A recent study suggested they have a protective effect.

Estrogen and Diabetes

• Postmenopausal women using low-dose therapy have a lower risk of having diabetes.

Estrogen Deficiency

• Estrogen deficiencies may have caused an accelerated aging process
• From 2003 studies over the past decade, many women may have died early without estrogen because of a hysterectomy.

Estrogen Replacement

• All methods of delivery are vital for assessing its safety.
• Should always be prescribed transdermally or through the vagina

Estrogen By Mouth

• Increases blood and triglycerides.
• Causes gallstones and elevated liver enzymes
• Lowers growth hormone
• Causes carbohydrate cravings and prothrombic issues.
• Raises estrone.

Study on Estrogen By Mouth

• Using oral estradiol vs using it through a patch has higher risks with thromboembolic issues.

Treatment with Estrogen

• Should be customized by a pharmacy
• May use different mixes of components for better results.

Progesterone in Women

• One of the two sex hormones.
• Up until menopause, it helps in the ovaries with function.
• Helps in different areas of the body like muscle, reproduction etc.

Functions of Progesterone

• Acts and functions as a Diuretic
• Anti-inflammatory
• Aids in Ovulation
• Balances estrogen
• Effects the potent action of GABA
• Balances cell action, and can decrease anxiety

Functions of Progesterone Continued

• Can regulate sleep
• Increases metabolism
• Increases scalp hair.
• Regulates the Hypothalamus
• Promotes a healthy breast and helps maintain implantation

Symptoms of Progesterone Loss

• Excessive mensuration
• Osteoporosis
• Insomnia
• Pain
• Irratability
• Depression

Causes of Low Progesterone

• Impaired production and lack of key hormones.
• Depression
• Sugar intake and little action
• The lack of key vitamins.

Synthetic Progesterone

• Can have negative affects and interfere with hormones
• Is found under a different name "progestins"

Side Effects of Progestins

• Causes a major change in mood
• Weight gain with constant need for eating
• Acne and hair loss.
• Major spike in breast cancer.

Estrogen Plus Progestin

• If used with some brands it can cause major issues with cancer

Natural Progesterone Effects Not Seen with Progestins

• Helps balance estrogen
• Leaves the body quickly.
• Protects breast health and gives immunity

Negative side Effects if High

• Weight gain plus it affects the bodies hormones, and the immune system is reduced.

Adrenaline

• Adrenaline interacts with progesterone.
• Surges may block progesterone, preventing its use.

Treatment with progesterone

• Progesterone can be compounded into a cream or capsule
• If the patient has an instance in sleeping, use oral to help their receptors

Progesterone and Breast Cancer Conclusion

• With the right amounts with tests you can really prevent chances of breast cancer.
• Studies have also shows that there has been a lack amount within the body.

Function of Testosterone in Women

• Increases sexual desire, sense of well-being, and muscle mass and strength.
• It helps to maintain memory, firms skin, reduces fat, and maintain bone strength.
• Elevates norepinephrine in the brain (antidepressant effect) and helps with pain control.

Symptoms of Testosterone Declines

• Muscle wasting can arise because of declines
• With low energy and memory are major causes
• Anxiety and fatigue. with low self esteem

What to test when low

• Menopause and childbirth
• With burnout and chemotherapy can really decline this production
• Endometriosis and medications.

Testosterone Treatments

• Has to mainly be treated to the skin and go along with key vitamins and food intake.
• Cannot be used alone, and be taken to account with your past.

Elevated Testosterone with Symptoms

• Can cause high levels of discomfort, with anger and irritability at high instances
• Weight gain with unwanted hair and risk of heart disease.

If To High What Treatment To Consider

• Many herbs and prescription medications and can help regulate this.

Testing Testosterone in women

• Androgens lead to many reproductive problems.
• Available androgen test, cannot prove results that can translate within.

SHBG

• SHBG carries E2 and testosterone.
• If there low there is little to non
• Drinking items with caffeine.

SHBG Continued

• Is linked from the PCOS
• The level may help what treatment and is need.

If High Wha To Due?

• If high, body doesn't work well so test your levels.
• Pregnancy can also change

Is High What To Do?

• Has to help bone structure and not cause harm in the body.

DHEA Facts

• Is key hormone in the brain
• With age it declines
• Changes in the bodies.

DHEA Functions

• Can help lose weight and help brain
• With its protection there are more benefits

Statin used on DHEA

• Statin drug usage can decline levels of these proteins

Causes with High DHEA

• Fatigue with anger

Cortisol

• With levels to increase in body it means it is a constant fight

Carl Sandburg

• Understand what kind of stress one can have and what you need to be able to do

Functions Of Cortisol

• Has major benefits from the brain to the heart

Cortisol

• Balances sugar with stress.
• Plays a part with sleep
• To function against in the body

What Do Cortisol Can Do Continued

• Is a mood enhancer when its low can cause you to have issues
• Causes many issues with body in a long term aspect

Causes With High Cortisol

• High Stress over time

Chronic Issues

• Causes heart rates and cause a major spike with problems.

Results of Elevated Cortisol

• If not monitored this one hormone can really shutdown all of your body in a negative approach.

DHEA Action In the Body

• Reduces high cholesterol and is good for the well being

DHEA is Helpful in A Few Areas

• Modulates the immune system while giving you support with fatigue and energy.

DHEA and Dosage

• The hormones should be taken with caution, and to look for what's is wrong and not hurt the body

Statin and DHEA

• A a study showed that SHBG levels in drugs were declining

DHEA Excess Causes

• Fatigue with agitation
• This can be caused with hair and sugar with all the issues that cause it

Adrenaline

• If not managed can cause the person to feel unwell all the time, and in general

What is a Treatment

• The replacement will help stabilize you back to normal

The Hormones

• Play a role with the proper synthesis while there actions need to have a normal basis

Insulin

• There has to be high standards with the body all the time

Insulin, The State

• Functions is also needed
• This has to be a concern.

Symptoms of Insulin Deficiency

• Bone loss and insomnia with this issue

The Causes Can be

• Long term poor diet habits
• To not have enough substance
• Exercising to much.

Excess Insulin Will Cause

• Problems and acne.

Insulin Can

• Worsen the situation when in a process of a slow process to the bad side

Excess Insulin is

• From excess or different diets
• Medications and to much of an intake for a need when it isn't asked for

Pregnenolone

• Made from cholesterol
• Decreases with your age

Benefits of Pregnenolone

• The overall balance that is between and a decrease on anxiety.

More and Results

• If people are predisposed with issues on memory a and with this you can make things less bad.

Benefits

• Help protect from cannabis

Caution

• As with all and or most hormones there may be a seizure if to much.

Major Symptoms with The use of this

• Issues and an abundance of levels of body issues.

Melatonin as a hormone

• Is tested to see if the balance is good, mainly in eye sight and brain.

Melatonin As The Guide

• High or low it plays a huge part into your brain to regulate hormones

Alcohol and More

• Caffeine will be a way it decreases and alcohol.

Melatonin Suppress

• Can mess up all levels
• Test it and see it

The Results are

• With this being in sync it is what plays the roles
• In short term is okay but long term is not.

Sleepy All Day

• There is really not that much of a need and a caution.

To The Foods

• These has levels of natural substance. In short make it balanced and know the risks.

What has to Be Considered

• St. Jonhs Work
• Being Caution and watch what you do.

With Testing

• Androgens show this if they are out of wack and cause major problems.

SHBG

• Is something used to see the testing on what levels are available.

Holtorf states

• With people doing bio chemical all clinical issues will decrease the potential for a patient to go into cancer

If you follow this then the end results are

• With what is going on as testing can only show in one way.

Take Away Point to This Information

• In these findings if there is something affecting you its because you have issues happening, and things need to be solved in all.